An Academic Research Enhancement Award (AREA) award to promote research at primarilyundergraduate institutions (PUIs) ?(R15) will greatly impact both my career goals and myundergraduate students and fully meet the intended purpose of this award. Specifically, this awardwould 1) allow me to pursue my continuing interest in metabolism as it relates to the normal anddiseased brain, 2) expose students to relevant research, and 3) support the commitment TrinityUniversity has for scientific research and discovery. During this award period students in my lab willbe afforded an exceptional opportunity to obtain training in the field of mouse genetics, corticaldevelopment and culturing primary neurons as well as astrocytes, which will enhance their interest inmolecular and cellular neuroscience. As a junior faculty member, this award will positively impact theachievement of my long term goals. As a new assistant professor, securing a prestigious award willbe pivotal in launching a successful career trajectory as a neurobiology researcher and professor at aPUI. My proposal focuses on AMPK in the nervous system. AMPK is a trimer composed of acatalytic subunit, ?, and two regulatory subunits, ? and ?. As an energy sensor and regulator ofmetabolism, AMPK would be expected to play a vital function during neuronal development,maintenance, and survival. However, to date the genetic analysis of AMPK? function in themammalian nervous system has not been explored. Therefore, this proposal aims to identifymolecular mechanisms AMP-activated protein kinase may play in the mammalian nervous system.We will specifically evaluate the in vitro effects of AMPK?1/?2 genetically null astrocytes in autophagyand apoptosis
The mammalian brain depends on a constant supply of glucose and oxygen. Lack of either one of them rapidlyleads to failure of neuronal function. The regulation of brain energy metabolism is accomplished via theconstant communication between astrocytes and neurons. Furthermore; the role of astrocytes in stroke andneurodegenerative processes is also becoming increasingly appreciated. Many of these neurological diseaseshave been implicated to be due to dysregulation of autophagy and energy metabolism. Model organism studieshave shown that AMP-activated protein kinase (AMPK) function is critical for neuronal maintenance. Lack ofAMPK function results in progressive neurodegeneration; which has implications for many neurodegenerativediseases including Alzheimer?s and Parkinson?s. Additionally; Ghrelin; an AMPK activator; has also been shownto play a role in various neurodegenerative processes; including AD; and Parkinson?s. Furthermore; Metformin isa widely used Type 2 diabetes drug shown to have its therapeutic effects through the activation of AMPK.Furthermore; rapamycin has been shown to be a potential therapeutic modulator for many neurodegenerativedisorders; such as Alzheimer?s; Parkinson?s; and Huntington?s.
